ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.4664T>A (p.Leu1555His) (rs1060501524)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563862 SCV000668129 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000563862 SCV000910268 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing
Counsyl RCV000462975 SCV000796969 uncertain significance Ataxia-telangiectasia syndrome 2018-01-05 criteria provided, single submitter clinical testing
Invitae RCV000462975 SCV000546651 uncertain significance Ataxia-telangiectasia syndrome 2017-05-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with histidine at codon 1555 of the ATM protein (p.Leu1555His). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in individuals affected with breast cancer (PMID: 19781682, 17393301). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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